Efficacy and effectiveness of COVID-19 vaccines in Africa: A systematic review

Background Data on COVID-19 vaccine effectiveness to support regional vaccine policy and practice are limited in Africa. Thus, this review aimed to evaluate the efficacy and effectiveness of COVID-19 vaccines administered in Africa. Methods We systematically searched peer-reviewed randomized controlled trials (RCTs), prospective and retrospective cohort studies, and case-control studies that reported on VE in Africa. We carried out a risk of bias assessment, and the findings of this review were synthesized and presented in a narrative form, including tables and figures. The synthesis was focused on COVID-19 VE against various levels of the disease condition and outcomes (infection, hospitalization or critical, and death), time points, and variants of concern. Results A total of 13 studies, with a total sample size of 913,285 participants, were included in this review. The majority (8/13) of studies were from South Africa and 38.5% (5/13) were randomized clinical trials. The studies reported that a full dose of Pfizer-BioNTech vaccine had a VE of 100% against COVID-19 infection by Beta (B.1.351) and Delta variants and 96.7% against hospitalization by Delta variant. The Johnson and Johnson vaccine had VE ranging from 38.1%-62.0% against hospitalization and 51.9%- 86% against critical disease by Beta (B 1.351) variant. The Oxford–AstraZeneca vaccine had a VE of 89.4% against hospitalization by the Omicron variant but was not effective against the B.1.351 variant (10.4%). The Sinopharm vaccine had a VE of 67% against infection and 46% against hospitalization by Delta variant. Conclusions COVID-19 vaccines administered in Africa were effective in preventing infections, hospitalization, and death. These review findings underscore the need for concerted efforts of all stakeholders to enhance the access and availability of COVID-19 vaccines and reinforce public awareness to reach the high-risk, unvaccinated group of the African population.


Introduction
The COVID-19 pandemic was one of the most devastating public health emergencies that the world faced in the 21 st century, which claimed the lives of millions of individuals, jeopardized the socio-economic and psychological well-being of the global communities, and severely impacted the health system, particularly in low-and middle-income countries [1,2].Fortunately, with the rapid advent and introduction of COVID-19 vaccines, it was possible to mitigate its further impacts-saving lives and livelihoods of the population [3,4].
However, due to the rapid discovery of the COVID-19 vaccines and the prevailing conspiracies on the quality and safety of the vaccines and misinformation, the vaccine uptake by the African population was limited [5,6].As of December 2023, 33% of African populations were vaccinated with a complete primary series of a COVID-19 vaccine and only 6% of the total African populations received booster COVID-19 vaccine.More importantly, as the clinical trials during the vaccine discovery were mainly conducted in developed nations' settings, there was hesitancy about its effectiveness in the African populations [7,8].Nevertheless, studies conducted on real-world vaccine effectiveness reflected varying effectiveness of different COVID-19 vaccine types.Different strains of the SARS-COV2 viruses also reflected varying levels of effectiveness [9][10][11].
In Africa, seven types of COVID-19 vaccines (Johnson & Johnson (Ad26.COV2.S), Astra-Zeneca (ChAdOx1 nCoV-19 vaccine), Sinopharm vaccine (BBIBP-CorV), Sinovac, Sputnik V, Pfizer-BioNTech (BNT162b2), and Novavax (NVX-CoV2373) vaccines) were introduced and administered to the populations [12].However, there is a paucity of aggregated data on COVID-19 vaccine effectiveness in African settings.Moreover, a comparative analysis of different vaccine types against variants of concern and various disease levels is imperative to design tailored regional vaccine policy and decision guidance in terms of optimal resource allocation.Evidence on VE might also help in building the capacity of Africa-led science and vaccine discoveries.We, therefore, conducted a systematic review to evaluate the efficacy and effectiveness of COVID-19 vaccines used in Africa and their effectiveness against infection, severity, and death due to SARS-COV2 variants of concern.

Search strategy
We conducted this review as two independent teams; the team from the Makerere University Infectious Diseases Institute and the team from the Africa Centers for Disease Control and Prevention (Africa CDC).We then combined the reviews into this one manuscript.With this approach, we improved the systematic review's reliability, reproducibility, validity, and quality.
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline to conduct this systematic review and report the review findings [13].
We searched MEDLINE (PubMed Central), EMBASE, Web of Science, Cochrane Library, Google Scholar, and direct Google searches for studies published from January 01, 2020 to December 10, 2023.We used keywords, free texts, and Medical Subject Headings (MeSH) terms to search for published articles from the databases.The keywords initially used for our preliminary searches were: COVID-19 vaccine, vaccination, SARS-COV-2 vaccines, effectiveness, efficacy, and Africa.We used the search terms included in the S1

Outcome
The outcome of the review was that vaccine efficacy and effectiveness were assessed and described by the studies in terms of the vaccine's ability to prevent infection and reduce severity (hospitalization) and ICU admission or death.The vaccine efficacy and effectiveness (VE) were expressed by 1-Odds Ratio*100, or 1 -Relative Risk*100, or 1-Hazard Ratio*100, or VE by percentage and 95% confidence interval (CI) or 1À risk among vaccinated risk among unvaccinated * 100.

Quality assessment of studies
The authors determined the risk of bias using the Joanna Briggs Institute (JBI) critical appraisal checklist for RCTs, cohort studies, and case-control (including test-negative design) studies.After the critical appraisal, a score of �70% was considered as "low risk", 50-69% was considered "medium risk", and <50% was considered "high risk" [14].

Data extraction, management and presentation
Based on the data extraction template recommended by the Cochrane Handbook for systematic reviews [15], the authors of the review have extracted data from the full text of the studies on research information (the type of research designs, geographical location of the study, year of publication, sample size of the study, and duration of the follow-up), characteristics of the participants (age, inclusion and exclusion criteria, comorbidity status, SARS-COV-2 strain), intervention (vaccine type, dose, time since administration of the vaccine), control (unvaccinated group characteristics), outcome (how they assessed vaccine effectiveness).
The authors decided the eligibility of each study to be included in the review by using the eligibility criteria.If any difference occurs about the inclusion of the studies into the review, another external person who is an expert in the area of study was consulted.We used reference managing software (Endnote Version 8.0) to manage data extraction.

Data synthesis
We conducted a descriptive narrative synthesis of eligible studies included in the review.We summarized the characteristics of the studies by country of origin, study design, vaccine type, and variant of concern.The synthesis was focused on COVID-19 vaccine efficacy and effectiveness against various levels of the disease condition and outcomes (infection, severity (hospitalization) or critical, and death) and variants of concern (e.g., Alpha, Beta, Gamma, Delta, Omicron).The vaccine efficacy and effectiveness against infection were defined as the risk reduction of infection due to SARS-CoV-2 among vaccinated individuals compared to unvaccinated individuals.The vaccine efficacy and effectiveness against hospitalization were determined as the risk reduction of hospitalization among vaccinated individuals compared to unvaccinated individuals.The vaccine efficacy and effectiveness in preventing death was defined as the risk reduction of deaths due to COVID-19 among vaccinated individuals compared to unvaccinated individuals.The review's findings were synthesized and presented in a narrative form, including tables and figures, to aid data presentation where appropriate.

Selection and identification of studies
The PRISMA flow diagram (Fig 1 ) presents the number of studies screened and assessed for eligibility, those included in the synthesis, and the reasons for excluding the studies.Our search brought 908 articles, of which 285 records were duplicates and thus removed.Another 588 articles were excluded after reviewing their title and abstracts.The full texts of the remaining 35 studies were assessed for eligibility, study designs, exposure, and outcome measurements of our interest.Based on this, 22 studies were excluded because they failed to fit with the eligibility criteria.After evaluating each study's score using the quality appraisal criteria, the studies were included in the systematic review.All the studies were scored as low risk of bias (S2 Table ).

Vaccine efficacy and effectiveness by vaccine types and variants of concern
In the included studies, COVID-19 vaccine efficacy and effectiveness vary by the vaccine types, time, and variants of concern (Table 3).The studies included in this review reported Ad26.COV2.S VE (Johnson and Johnson) vaccine effectiveness ranges from 38.1% to 62.0% against hospitalization and 51.9% to 86% against critical disease (ICU admission) for a Beta (B 1.351) variant SARS-COV-2.

Discussion
COVID-19 vaccines played pivotal roles in the efforts to mitigate the pandemic.With the rapid advent and introduction of the COVID-19 vaccines, several millions of lives were saved, the psycho-social and economic well-being of the people was restored, and the health system was brought back to normal [4,10].However, challenges due to emerging and re-emerging variants of concern (VOC) and the decline of vaccine effectiveness over time (vaccine waning) have posed difficulties in vaccination programs [30,31].In Africa, where resources are limited and the health literacy level of the populations is minimal, COVID-19 vaccines might not optimally bring the desired changes.Therefore, we conducted a systematic review to evaluate the effectiveness of COVID-19 vaccines against infection, hospitalization (severity), and death.The principal findings of this systematic review revealed that the full doses of the vaccines administered in Africa were effective against the major variants of concern of SARS-COV-2.A full dose of the BNT162b2 (Pfizer-BioNTech) vaccine was found to have an effectiveness of 100% against COVID-19 infection by Beta (B.1.351)   of the vaccine type, that is most effective for the populations of Africa, and the appropriate allocation of resources.
Vaccine effectiveness studies, however, may be affected by various biases that may affect their findings [32,33].Observational studies are prone to confounding bias, although studies often address this concern.Biases in VE studies can also be introduced during outcome ascertainment and selection of participants (e.g., case-control or cohort studies).Differential testing methods among vaccinated and unvaccinated individuals could also contribute to the biased estimate of VE.Differential depletion of susceptibles-when the vaccine is effective, the people who are infected are more likely to be unvaccinated than vaccinated-could down-estimate the VE.The effect of treatments and passive prophylaxis on VE was not optimally assessed and might have effects on VE.Hence, the findings of the VE studies should be interpreted with caution-having in mind these biases that can be introduced to the studies.
The effectiveness of the vaccines increases with an increase in the recommended vaccine dosage; better prevention in 2 nd (complete primary series dose) and booster doses can be achieved than in the 1 st dose [34,35].Moreover, vaccines are more effective against severe and critical diseases than mild or asymptomatic infections-for instance, Johnson and Johnson Ad26.COV2.S vaccine effectiveness against moderate to severe-critical COVID-19 was 56.3%, 74.6% against severe-critical COVID-19, and 82.8% against COVID-19-related death.Therefore, enhancing public awareness to continue taking 2nd and booster doses to benefit from the vaccines optimally is critical.
Time after vaccination is also an important parameter reported to influence vaccine effectiveness.As the time interval increases, the vaccine efficacy decreases, and the probability of acquiring infection or worsened severity would be high [36,37].A study conducted in Morocco indicated that the Sinopharm vaccine would provide high and stable protection during the first three months (VE of 75%-88%) and decrease after the fourth month (VE of 64%) [27].Time after vaccination can be lengthened partly by the limited availability of vaccines in the vaccination centres or partly due to the patient's unwillingness to receive further dose(s).Notably, it is important to comply with the vaccination intervals recommended by each vaccine developer, and the general public needs to be aware of it.
This systematic review has some limitations.Two of the multinational studies, which have recruited participants from South Africa, were excluded from this study as they did not report South Africa-specific VE.Articles only published in English language were included in this study and we might have missed studies published in other languages.The risk of bias tool might not optimally capture vaccine effectiveness biases that might be introduced in the specific studies included in this review.Most of the studies were concentrated in a few countries (South Africa and Egypt) and might not represent the actual situation in the entire continent.Most RCTs were conducted in the earlier phases of the COVID-19 pandemic and might not adequately reflect VE for the Omicron variant.Therefore, we recommend further real-world vaccine effectiveness studies in Africa to address this gap.

Conclusions
This systematic review has revealed the high vaccine effectiveness of COVID-19 vaccines administered in Africa, particularly the commonly used Ad26.COV2.S VE (Johnson and Johnson) vaccine and Oxford-AstraZeneca vaccine (ChAdOx1/nCoV-19) vaccines.These review findings underscore the need for concerted efforts of all stakeholders to enhance the access and availability of COVID-19 vaccines and promote public awareness to reach the high-risk, unvaccinated group of the African populations.Further real-world COVID-19 vaccine effectiveness studies are also required in African settings.

Table 2 .
(Continued) * Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA-The finding included is South Africa-specific VE ** USA, South Africa, Brazil, Colombia, Argentina, Peru, Chile, Mexico-The finding included is South Africa-specific VE *** USA, Brazil, South Africa, Argentina, Turkey, Germany-The finding included is South Africa-specific VE https://doi.org/10.1371/journal.pone.0306309.t002 and Delta variants and 96.7% against hospitalization due to Delta variant.The Ad26.COV2.S (Johnson and Johnson) vaccine had a VE of 94.2% against infection caused by the Alpha (B.1.1.7)variant of SARS-COV-2 and 38.1% to 72.0% VE against hospitalization by B.1.351variant of SARS-COV-2.The Oxford-AstraZeneca vaccine (ChAdOx1/nCoV-19) had a VE of 89.4% against hospitalization by the Omicron variant of SARS-COV-2.However, the Oxford-AstraZeneca (ChAdOx1/nCoV-19) vaccine was not effective against the B.1.351variant (10.4%).The Sinopharm vaccine (BBIBP-CorV) had a VE of 67% against infection and 46% against hospitalization by Delta variant.The disparities in VE by vaccine types and variants of concern have implications for the identification